Process of preparing pyridylmercuric salts



y 2, 1940- R. N. SHREVE :1- AL 2,206,309

PROCESS OF PREPARING PYRIDYLMERCURIC SALTS Filed June is, 1938 FIG}.

PER CENT YYII Flea;

TIME IN HOURS PER CEN YIELD TIME IN HOURS .FIG.3.

? PERCENT ELD Patented July 2, 1940 UNITED STATES PROCESS OF PREPARING PYRIDYL- MERCURIOSALTS 1 Randolph Norris Shreve, West Lafayette lnd and Maxwell James Skeeter Pittsburgh, Pa.,

assignors to Mallinckrodt Chemical Works, St. Louis, Mo., a corporation of Missouri Application June 16, 1938, Serial No. 214,060

Z Claims. (o1. zen- 270) This invention relates to processes of mercurating pyridine, and, with regard to certain more specific features, to processes of preparing pyridylmercuric salts.

5 Among the several objects of the invention may be noted the provision of an economical process of preparing pyridylmercuric salts from commonlyavailable, economical raw materials, with relatively high yields of such saltsin any desired condition of purity. Other objects will be in part obvious and in part pointed out hereinafter,

The invention accordingly comprises the steps and sequence of steps, and features of procedure,

which will be exemplified in the processes hereinafter. described, and the scope of the application of which will be indicated in the following claims.

Figures 1, 2, and 3 of the accompanying drawing are graphs illustrating certain relationships hereinafter to be explained.

The mercuration of pyridine with mercuric acetate has heretofore beenldescribed by Mc- Cleland and Wilson in the Journal of the Chemical Society, London, 1932, part I, pages 1263-1265. The McCleland and Wilson procedure was to heat 5 mercuric acetate (1000 g.) with pyridine (200 c. c.) in an autoclave at 180 C. for 2 hours, then to filter oh. the insoluble residue, dilute the liltrate, and precipitate the pyridylmercuric chloride from the filtrate by adding an excess of sodium chloride solution. i

While this process operates in the manner stated by the authors, its yields are so meagre that it is practically a prohibitively expensive method. We have repeated the McClelandand Wilson process many times, and have not at any time been able to obtain a yield of pure pyridylmercuric chloride of greaterthan about "7% of the theoretical yield, based upon the amount of mercuric, acetate used. In their article, ,Mc-

) Cleland and Wilson indicate a 27.55% yield of crude pyridylmercuric chloride, and a yield of 6.89% of pure pyridylmercuric chloride, on the same basis, but we have been unable to obtain any such yields of crude material following the directions of McCleland and Wilson.

One of the principal objects of the present invention, therefore, was to determine, if possible, what factors were operating to reduce the yield of the McCleland-Wilson process to so low a value, and then to determine the proper conditions for bettering such yields. This we have succeeded in doing, as explained in detail hereinafter, and. our process, consequently, brings about commercially entirely practicable yields. 3

A first approach to the problem of low yields was made along the line that the insoluble residue formed in the McCleland-Wilson process was itself suppressing the yield of the desired pyridylmercuric salt. Investigation of this insoluble residue shows that it is probably a mixture of highly solubleresidue.

complex polymercurated pyridine compounds, corresponding to formulae such as mcoooH HaCCOOHg LN HgCOOCH: or r it lIaCOOOHgfiHf-fiEIgOOOCHs h H OCOOHgLN HgiN or The presence of such complex compounds would certainlyreduce the yield of the desired pyridyl mercuric salts, because of their consumption of large amounts of the available mercury.

A first aimof our work, therefore, was to eliminate or at least reduce the formation of this in- HgOOOOHa Earlier work seemed to indicate that, in the mercuration reaction, no coupling of the mercury to the pyridine took place until after the commencement of the formation of the insoluble residue. However, further experimentation revealed that this was not the case, and that, in all probability, amajor portion of the insoluble residue was formed by reaction of the alreadyformed pyridylmercuric acetate with further pyridine and mercuric acetate. We accordingly tried an experiment in which the heating of the reaction mixture was discontinued immediately upon, the commencement of the formation of the insoluble residue, For example, in a reaction mixture consisting of 25 grams of mercuric acetate and 50 c. c; of pyridine (the proportions used by McCleland and Wilson), heated at 180 C. in an autoclave, the insoluble residue cornmenced to form in about 32 minutes, and the yield of crude pyridylmercuric chloride, stopping the reaction after32 minutes, was 18.5%, against the 7% yield following the directions of Mc- Cleland and Wilson. Prolonging the heating period beyond 32 minutes results in the formation of ever-increasing amounts of insoluble residue, and in ever-decreasing yields of pyridylmercuric chloride.

, It is accordingly a first feature of our process to discontinue the heating of the reaction mixacetate) ture, and hence to disoontinuethe reaction, substantially immediately upon the formation therein of any insoluble residue.

While the yield is thus improved,

next a series of experiments to determine the ef-= fect of varying reaction temperatures upon the yields.

Numerous batches of reaction mixture were made up, each comprising 15 grams of mercuric acetate and 30 c. c. of pyridine. heated at various temperatures for various lengths of time in an all-glass autoclave, sothat the point of the commencement of the formation of the insoluble residue could be noted. The reaction mixtures were then treated to recover crude pyridylmercu'ric chloride by a procedure hereinafter to be described, and the yields calculated. The results are plotted in graph form in Fig. 1. Three curves are shown, one each for reaction temperatures of 180, 170, and 160. On each curve, an r indicates the time at which the formation of insoluble residues commenced. It will be noted that the maximum yield in each instance occurs at the at point, offering further confirmation of the aforementioned first feature of the invention.

The maximum yield, it will be noted, increases as the temperature of the reaction is decreased. However, attempts to repeat the experiments at temperatures below 160 (at 155, for example) resulted in no appreciable mercuration of the pyridine. y

A second feature of the invention accordingly comprises carrying out the reaction at the lowest temperature at which it will proceed (160 in the case of a simple mixture of pyridine and mercuric Thus is the yield of pyridylmercuric chloride somewhat higher. 7

Attempts were made to increase the yield of pyridylmercuric chloride by varying the proportions of the reactants. In general such attempts showed that the ratio we had been using was an optimum ratio, for while an increased dilution with pyridine increased the yields of pyridylmercuric chloride slightly, it also caused the undesirable formation during the reaction of mercuric oxide, and an increased concentration of mercuric acetate in the reaction mixture distinctly depressed the yield.

For further enhancing the yield, we undertook a series of experiments in which we added water to the reaction mixture. For our initial experiments, we used mixtures in which the water was added in equal molecular proportion with the pyridine. The first series of runs were conducted at 170, 165, and 160, the temperatures found most satisfactory in the previous study of the effect of temperature upon the reaction. The results are plotted as appropriately-indicated curves in Fig. 2. Again at indicates the pointat which the formation of insoluble residue commences, and this point, it will be noted, approximately coincides with the point of maximum yield, as heretofore.

With the added water, however, it becomes pos-. sible satisfactorily to carryout the reaction at temperatures below 160, and thecurves corresponding to such temperatures (155, 150, and are shown in Fig. 2. It will at once be noted that the 155 curve shows a maximum yield (just under 50%) that is by far the highest yield yet obtained in the reaction, and that this yield is considerably greater even than the maximum yields of the nearest adjacenttemperatures it is still not entirely satisfactory. We accordingly undertook increases the yield so markedly, but it is probably These were and 160). It therefore appears that or close to this temperature, is the particular optimum temperature, under the given conditions, to carry out the reaction.

It is not entirely clear as to just why the water because the water tends to retard the formation of the highly complex polymercurated pyridines, thus making more of the mercuric salt available for the desired monomercuration.

lit will be noted that one effect of the addition of water is to prolong the duration of the reac- I tion prior to the appearance of insoluble residues, which is also the approximate point of maximum yields. This fact tends to support the retardati'on theory of the preceding paragraph. The prolon'gatiomhowever, is not serious from the standpoint of cost, as but 2% hours are needed to obtain maximum yield at optimum temperature (155).

Still another series of experiments was run to determine the optim'um amount of water for the reaction mixture. In these experiments, the amounts of pyridine and mercuric acetate in the reaction mixture were held constant, but the amount of water (in molar ratio to the mercuric acetate) was varied. All reactions were carried out at 155, and were stopped after 2 hours. The yield of each experiment was determined, and the results plotted as the curve of Fig. 3. It will at once'be seen that a water-to-mercuric acetaternol'ar ratio of about 8 is productive of maximum yields. This is the same as the equimolar ratio of water to pyridine as used in the preceding series of experiments.

From all of the foregoing, it will be seen that we have established, as the several criteria for optimum yield of pyridylmercuric chloride, the following:

(1) The reaction mixture should be made up of equimolar parts of pyridine and water, and a portion ofmerciiric acetate sufficient to make the water (or pyridine) to mercuric acetate molar ratioequal to about 8.

2) The reaction shouldbe carried out at close to 155.

(3) The reaction should be continued only un- I acted mercuric acetate prior to the precipitation of the pyridylmercuric chloride, is as follows:

After the reaction has been carried out in the autoclave for the desired time, the residue is filtered off from the reaction mixture. The filtrate is then transferred to a vacuum still, where about two-thirds ofthe excess pyridine is distilled off at as high a vacuum as conveniently possible (say, 730 m. m. of mercury). The residue may advantageously be washed withwater in the meanwhile, and the wash water used to wash the residue I (a viscous syrup) from the still. The solution is then diluted with water, and an excess of acaustic solution (such as sodium or potassium hydroxide) is added and the. agitated only objection to this method is slow filtration of allowed to settlefor a few hours.

.mercuric acetate one-half hours.

soluble residue syrup, is washed from the with strong agitation. The caustic brings about the precipitation of the unreacted mercuric acetate, residual tars, and to some extent any lower polymercurated pyridine compounds present by reason of their solubility inpyridine. After allowing the precipitate to settle out, it is filtered 01f, and the filtrate is desirably clarified with decolorizing carbon. Then the filtrate is brought back to its original acidity and diluted again with water. Sodium chloride solution is then added, preferably dropwise and with constant agitation, until it is in excess. This causes the precipitation of crude pyridylmercuric chloride, which is preferably allowed to settle for 18 to 24 hours prior to filtering it oii. The product is then dried at. 125, and it may bepurified by recrystallization if necessary.

If other salt solutions, such as sodium nitrate, are used inplace of the sodium chloride, the products are correspondingly other pyridylmercuric salts, such as the nitrate, or if the clarified filtrate is evaporated and crystallized out without the addition of any salt, the product is pyridylmercuric acetate.

With the foregoing criteria in mind, we have worked up a preferred manner of carrying out the process of the present invention, utilizing the various features of the invention as hereinbefore pointed out. This preferred process is as follows:

An autoclave is charged with pyridine (8 mols.), agitation isstarted, and mercuric acetate (1 mol.) added. Agitation is continued until the is entirely in solution. Water (8 mols.) is added and the autoclave sealed. Heat is applied, raising the temperature as rapidly as possible to 155 0., where it is held for two and The autoclave is then allowed to cool and contents pumped to a filter. At this point, in plant operation, it may be advisable to add a chloride free filter aid to the charge and/or to precoat the filter, since the first formed inis very fine and gummy.

The filtered charge is run to a vacuum still and the press is washed with water, which has previsly been used to wash out the autoclave, and the wash sent to the caustic treatment tank.

The charge in the vacuum still is then distilled under high vacuum (730 mm.) until about twothirds of the excess pyridine is removed. The residue, which is now in the form of a viscous still into the caustic treatment tank. The combined still residue solution and wash water from the autoclave and press is diluted to about ten times its original volume (as charged into autoclave) and caustic soda (1 mol.) in solution, is slowly added, with good agitation.

At this point there are two likely methods of handling the charge:

(1) Decolorizing carbon maybe added directly charge filtered at once. (The the entire charge.)

(2) Agitation may be stopped and the charge The clear liquor and lower polymay be siphoned off. The then filtered, the filtrate added above the settled mercuric oxide mercurated products settled residue is to the bulk of the charge and then clarified.

Following either of the above steps, the precipitated residue is dissolved in acetic acid, reprecipitated with caustic, and filtered, following the The agitation is continued for one hour after the caustic addition.

procedure above. This step is to free any oceluded acetate. The filtrate is combined with the first filtrate and sufficient acetic acid is added to neutralize the caustic. After neutralization, the

3-pyridylmercuric acetate is precipitated as 3- pyridylmercuric chloride by the slow addition of a saturated sodium chloride solution while the solution is thoroughly agitated.

The precipitated charge is then pumped to an unagitated tank where it is allowed to stand for twenty-four hours to complete the precipitation of the chloride.

When precipitation is complete, the charge is filtered and washed. The crude may then be dried at 125 C. or, if desired, may be purified by recrystallizing twice fr in aqueous pyridine and once, from water.

The crude product is fluxings and crystallizations from, first, 25% aqueous pyridine; second, 10% aqueous pyridine; and third, distilled water, with decolorization by means of carbon.

In the first crystallizations from the aqueous pyridine solutions the product is sometimes low (65%). However, when the mother liquor from the first recrystallizations is used as the solvent for succeeding recrystallizations very good yields In the experimental work recoveries of 98.2%, 92.8% and 98.0% on the first, second, and third crystallizations, respectively, were obtained.

As i to equipment, it seems advisable to use either a glass lined or some other type of vitreous or enamelled autoclave. Iron, if present, tends to decreasethe yields, and brass is corroded by the reaction mixture. A similar consideration applies to the filters and other treating equipment.

In general, the pressures in the autoclave during the reaction are only those set up by the reaction itself. Such pressures generally run about '75 pounds per square inch.

In View of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained.

As many changes could be made in carrying out-the above processes without departing from the scope of the invention, it is intended that all matter contained in the above description shall be. interpreted as illustrative and not in a limiting sense. i i

We claim:

2. The process of preparing C-pyridylmercuric salts, which comprises heating pyridine and a mercuric salt together in the presence of water, at a temperature of about 155" C., until thedesired C-pyridylmercuric salt is formed, and discontinuing the heating substantially immediately upon the commencement of the formation of an insoluble residue in the reaction mixture, and

recovering the desired C pyridylmercuric salt from the reaction mixture.

.RANDOLPH NORRIS SHREVE.

MAXWELL JAMES SKEETERS.

are invariably obtained.

substantially impurified by successive rerecovery of crystallized 

